Kengo Shibata, Cheng Chen, Xin You Tai, Sanjay G Manohar, Masud Husain
{"title":"APOE、Klotho 和性别对老年认知能力下降的影响","authors":"Kengo Shibata, Cheng Chen, Xin You Tai, Sanjay G Manohar, Masud Husain","doi":"10.1101/2024.07.20.24310745","DOIUrl":null,"url":null,"abstract":"The effects of APOE and Klotho genes, both implicated in aging, on human cognition as a function of sex and age are yet to be definitively established. Here we showed in the largest cohort studied to date (N = 320,861) that APOE homozygous ε4 carriers had a greater decline in cognition with aging compared to ε3 carriers (ε4/ε3 & ε3/ε3) as well as smaller hippocampi and amygdala (N = 37,976). Critically, sex and age differentially affected the decline in cognition. Younger (40 - 50 years) female homozygous ε4 carriers showed a cognitive advantage over female ε3 carriers, but this advantage was not present in males. By contrast, Klotho-VS heterozygosity did not affect cognition or brain volume, regardless of APOE genotype, sex or age. These cognitive trajectories with aging demonstrate clear sex-dependent antagonistic pleiotropy effects of APOE ε4, but no effects of Klotho genotype on cognition and brain volume.","PeriodicalId":501025,"journal":{"name":"medRxiv - Geriatric Medicine","volume":"181 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of APOE, Klotho and sex on cognitive decline with aging\",\"authors\":\"Kengo Shibata, Cheng Chen, Xin You Tai, Sanjay G Manohar, Masud Husain\",\"doi\":\"10.1101/2024.07.20.24310745\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The effects of APOE and Klotho genes, both implicated in aging, on human cognition as a function of sex and age are yet to be definitively established. Here we showed in the largest cohort studied to date (N = 320,861) that APOE homozygous ε4 carriers had a greater decline in cognition with aging compared to ε3 carriers (ε4/ε3 & ε3/ε3) as well as smaller hippocampi and amygdala (N = 37,976). Critically, sex and age differentially affected the decline in cognition. Younger (40 - 50 years) female homozygous ε4 carriers showed a cognitive advantage over female ε3 carriers, but this advantage was not present in males. By contrast, Klotho-VS heterozygosity did not affect cognition or brain volume, regardless of APOE genotype, sex or age. These cognitive trajectories with aging demonstrate clear sex-dependent antagonistic pleiotropy effects of APOE ε4, but no effects of Klotho genotype on cognition and brain volume.\",\"PeriodicalId\":501025,\"journal\":{\"name\":\"medRxiv - Geriatric Medicine\",\"volume\":\"181 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-07-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"medRxiv - Geriatric Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.07.20.24310745\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"medRxiv - Geriatric Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.07.20.24310745","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Impact of APOE, Klotho and sex on cognitive decline with aging
The effects of APOE and Klotho genes, both implicated in aging, on human cognition as a function of sex and age are yet to be definitively established. Here we showed in the largest cohort studied to date (N = 320,861) that APOE homozygous ε4 carriers had a greater decline in cognition with aging compared to ε3 carriers (ε4/ε3 & ε3/ε3) as well as smaller hippocampi and amygdala (N = 37,976). Critically, sex and age differentially affected the decline in cognition. Younger (40 - 50 years) female homozygous ε4 carriers showed a cognitive advantage over female ε3 carriers, but this advantage was not present in males. By contrast, Klotho-VS heterozygosity did not affect cognition or brain volume, regardless of APOE genotype, sex or age. These cognitive trajectories with aging demonstrate clear sex-dependent antagonistic pleiotropy effects of APOE ε4, but no effects of Klotho genotype on cognition and brain volume.
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